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Prediabetes, Type 2 Diabetes Come With Altered Gut Microbiomes

NEW YORK – The gut microbiome is altered in people with prediabetes or type 2 diabetes, a new analysis has found.

About a third of adults in the US and one in 14 worldwide are thought to have prediabetes, which is marked by higher-than-usual blood glucose levels that don't reach the criteria for type 2 diabetes. While lifestyle changes, bariatric surgery, and medication can forestall disease progression, up to 70 percent of people with prediabetes eventually develop type 2 diabetes.

 A team of researchers in Sweden has now profiled the gut microbiomes of more than 1,000 Swedish individuals who they grouped according to their blood glucose testing results. The microbiomes of individuals with impaired glucose tolerance, combined glucose intolerance, and type 2 diabetes differed from those with normal glucose tolerance, as the researchers reported in Cell Metabolism on Friday. The level of butyrate-producing bacteria was lower in both the prediabetes and type 2 diabetes (T2D) groups, suggesting a possible role for butyrate producers or butyrate in disease development.

"Our study indicates that the gut microbiome represents an important modifiable factor to consider when developing precision medicine approaches for the prevention and/or delay of T2D," the University of Gothenburg's Fredrik Bäckhed and his colleagues wrote in their paper.

The researchers enrolled 1,011 individuals into their discovery cohort based on their fasting and two-hour oral glucose tolerance test results. In this set, 523 individuals had normal glucose tolerance; 189 had impaired fasting glucose; 178 had impaired glucose tolerance; 75 had combined glucose intolerance; and 46 had treatment-naïve T2D. About half the individuals with normal glucose tolerance were at high risk of developing diabetes based on lifestyle factors and family history.

Using whole-genome shotgun sequencing, the researchers profiled the microbiomes of stool samples obtained from these individuals. Based on a PCA analysis, they noted a significant separation of the composition of the gut microbiomes of the groups with impaired glucose tolerance, combined glucose intolerance, and T2D from the low-risk normal glucose tolerance group.

A similar pattern was observed in their validation cohort of 484 individuals. 

Previous studies, the researchers noted, had suggested a difference between the microbiomes of people with and without T2D, but those analyses may have been influenced by the inclusion of patients on metformin or other drugs to treat diabetes. In this study, the researchers found that the effect is independent of those drugs.

They also developed a random forest algorithm-based classifier to distinguish people with combined glucose intolerance or T2D from those with normal glucose tolerance, based on the characteristics of their microbiomes. The classifier had moderate prediction power, which they boosted with the addition of other diabetes risk factors, such as lifestyle.

The abundance of nearly 120 metagenomic species differed between the groups with affected glycemic status, as compared to those with normal glucose tolerance and low disease risk. Thirty-eight of these species contributed to the classifier.

Further, nearly half the differentially abundant species were potential butyrate producers, 14 of which contributed to the classifier. Most of the potential butyrate producers — such as Faecalibacterium, Clostridium, and Alistipes species — decreased in abundance in the groups with affected glycemic status. The researchers noted that the abundance and function of butyrate producers is modulated by diet, especially fiber intake, and suggested there may be a causal role for butyrate or its producers in the etiology of glucose intolerance or the progression toward T2D.

"Future studies should test whether restoration of altered microbial functions, such as butyrate production, in individuals with [impaired glucose tolerance] and [combined glucose intolerance] might constitute a precision medicine approach to prevent or delay the progression to T2D," the researchers wrote.